The unfolded protein response sensor PERK mediates mechanical stress‐induced maturation of focal adhesion complexes in glioblastoma cells

Abstract

Stiffening of the brain extracellular matrix (ECM) in glioblastoma promotes tumor progression. Previously, we discovered that protein kinase R (PKR)‐like endoplasmic reticulum kinase (PERK) plays a role in glioblastoma stem cell (GSC) adaptation to matrix stiffness through PERK/FLNA‐dependent F‐actin remodeling. Here, we examined the involvement of PERK in detecting stiffness changes via focal adhesion complex (FAC) formation. Compared to control GSCs, PERK‐deficient GSCs show decreased vinculin and tensin expression, while talin and integrin‐β1 remain constant. Furthermore, vimentin was also reduced while tubulin increased, and a stiffness‐dependent increase of the differentiation marker GFAP expression was absent in PERK‐deficient GSCs. In conclusion, our study reveals a novel role for PERK in FAC formation during matrix stiffening, which is likely linked to its regulation of F‐actin remodeling.